This invention concerns silicon dioxide-containing compositions and a process for the preparation thereof whereby active materials are incorporated therein such that the active materials are stabilized and/or their rate of liberation is controlled.
In formulating active materials, especially pharmaceutical or pest combating agents, various processes have been employed to mask flavor, reduce volatility, stabilize against oxidative and/or hydrolytic decomposition, achieve better handling during production and administration etc. Recently, measures to control the rate of liberation of active materials, i.e., to achieve a desired retarding has received much attention, e.g., for the production of depot pharmaceuticals. The most important retardation technique involves binding of the active material to carrier substances or embedding of the pharmaceuticals in suitable encapsulating or matrix substances.
When embedding into a matrix or binding onto a carrier via asorptive forces or ion exchange is employed, in addition to a large number of organic adjuvant materials (macromolecules, fats), inorganic materials such as barium sulphate, calcium sulphate, calcium phosphate, titanium dioxide and the like are also recommended. However, for the encapsulating of particles, organic substances, mostly natural, semi-synthetic or synthetic macromolecules, are used exclusively. A large range of suitable adjuvant materials is thereby available, comprising essentially hydrophilic colloids, such as gum arabic, gelatine, cellulose ethers or swellable materials, such as methacrylic acid derivatives, cellulose esters, as well as plastics, such as PVP, polyamide, polyethylene, polyacrylates, polystyrene and a series of other mixed polymers.
In spite of this multiplicity of adjuvant materials, and of a highly developed technology, conventional formulations exhibit a series of disadvantages which, in part, considerably limit their application and also lessen the reliability of achieving the desired liberation features. This is especially true for conventional depot formulations.
On the other hand, especially when organic adjuvant materials are used, liberation of the active material in the gastrointestinal tract is very difficult to control. This disadvantage is due to the fact that the liberation of the active material by diffusion from a matrix or through porous capsule walls or after dissolution of an encapsulating material, is very considerably dependent upon the conditions of the surroundings, such as e.g. pH, ion concentration, enzyme influences and the like. Due to these conditions, dissolution or swelling of the matrix or enveloping substances often occurs, whereby the ensuing nature and rate of liberation of the active material often cannot be anticipated. In many cases, the complete availability of the active materials is impaired by binding to carriers, whereby exact dosaging becomes difficult.
On the other hand, compatibility of the active material with the carriers is often unsatisfactory, especially in the pharmaceutical field. For example, the adjuvant materials can burden the digestive tract or may even be fully incompatible for certain patients, e.g., those who must avoid sugars, fats, etc. Moreover, due to expansion and/or swelling of materials, unpleasant feelings of satiation can be produced and even potential danger can exist if the polymers used still contain residual parts of toxic components, such as, e.g., catalysts, accelerators, hardeners, plasticisers, stabilizers, filling materials or unreacted monomers.
Furthermore, due to the very large number of recommended adjuvant and additional materials, an enormous number of combinations are possible. Consequently, the development of a pharmaceutical form for a new active material becomes a time-consuming and expensive proposition. In addition, the formulation process itself, e.g, microencapsulation, requires a high degree of precision with attendant complicated and expensive apparatus when reproducable results are required.